The purpose of this study is to examine the role of serum brain-derived neurotrophic factor (BDNF) as a potential biomarker for the response to neuroplasticity-based cognitive remediation in patients with schizophrenia. We are requesting a modest amount of supplemental funding to our original RO1 grant, Cognitive Remediation in Schizophrenia (grant period 2004-2009). The requested supplement grant will be used to obtain and process a series of blood samples for serum BDNF levels from schizophrenia subjects enrolled in a randomized trial of intensive, computerized, neuroplasticity-based cognitive training exercises, as well as healthy comparison subjects matched on age, gender, and IQ. Supplemental funds will be used to analyze BDNF levels in stored serum samples from all current subjects as well as to gather additional samples form these and future incoming subjects. The serum BDNF results will be analyzed with respect to longitudinal clinical and neurocognitive data being obtained in the parent study. [unreadable] [unreadable] We study is supported by pilot data from our first cohort of schizophrenia subjects who have completed 50 hours of intensive neuroplasticity-based cognitive training exercises. Serum BDNF levels were increased by 30% in 15 subjects who underwent 12 weeks of the training, but not in 11 subjects who underwent the active computer games control condition (change measures significantly different between the two groups, p<0.05). Statistically significant associations were present between changes in serum BDNF levels and measures of working memory and learning after the cognitive training, consistent with a trophic response in hippocampal and cortical neurons as a result of the intensive training. The specific aims of this study are thus: 1) To obtain measures of serum BDNF levels on each subject at 5 time points at study entry, and then after 2, 10, and 20 weeks of intervention, as well as at 6-month follow- up; 2) To examine the relationship of baseline serum BDNF levels to baseline neurocognitive function in schizophrenia subjects and in healthy comparison subjects; 3) To examine the relationship of change in serum BDNF levels to change in neurocognitive function in the two groups of schizophrenia subjects, those undergoing neuroplasticity-based targeted cognitive training (N = 40) as compared to those undergoing a computer games control condition (N = 40). PUBLIC HEALTH RELEVANCE: This purpose of this study is to investigate the relationship between serum levels of brain-derived neurotrophic factor (BDNF) and response to neuroscience-guided cognitive remediation in patients with schizophrenia. BDNF is a factor that promotes the health and functioning of neurons, plays a key role in learning, and enhances the brain's resiliency to stress. We will investigate whether measures of serum BDNF can serve as a biomarker for observed improvements in cognitive functioning in schizophrenia subjects who are undergoing an intensive computerized cognitive remediation program. [unreadable] [unreadable] [unreadable]